Based on the working hypothesis that mutagenesis is responsible for tumor initiation and gene modulation is the cause of tumor promotion and antipromotion, we have proposed to develop an in vitro Chinese hamster system to distinguish carcinogenic agents which act either as mutagens or gene modulators. We propose to verify the potential of this in vitro assay system by (a) systematically testing a number of known tumor promoters and anti-promoters; (b) correlating the mutation modifying experiments with the induction or repression of ornithine decarboxylase; (c) studying the possible biochemical mechanism(s) of tumor promotion and anti-promotion; (d) studying the phenomenon of "co-mutagenesis" to see if it might be correlated with "co-carcinogenesis"; (e) applying the in vitro mutation assay to determine its practical potential (i.e., to test saccharine); and (f) developing a human fibroblast assay system to be analogous to the Chinese hamster system.